Alterations of composition and pressure of the respiratory gases may induce lethal intoxication or can sustain life in unusual environments or in disease. Within the narrow range of oxygen pressures tolerated by living cells, the processes of cellular oxidation and energy metabolism depend upon effective delivery of oxygen to the metabolic site and the balance of oxidant-antioxidant processes. Inadequate tissue oxygenation limits the ultimate oxidation process. Excessive oxygenation, as in therapeutic or other use of high oxygen pressures, disrupts the enzyme activity upon which oxidation itself depends. Both oxygenation and oxidation processes and even the poisoning by hyperoxia are affected by exposures to extreme alterations of carbon dioxide, inert gases, and certain respired toxic gases. This program of interrelated studies is therefore concerned with respiratory, cardiovascular, gas transport and metabolic influences of both low and high oxygen pressures in health and disease and the interrelationships of respiratory gas effects upon vital functions. In these investigations of metabolically active and inert respiratory gases, emphasis is given to dose-response studies to elaborate the progressive effects of and limits of tolerance to increasing partial pressures or density of the respiratory gases. Adaptations and deteriorations of sensory, cognitive, neuromuscular, pulmonary, respiratory, cardiovascular and exercise functions are quantitatively determined to provide the bases both for elucidating mechanisms of gas effects and predicting the consequences of complex exposures. Investigation of inert gas exchange in organs and tissues further provides the basis for development of systems of decompression from exposure to high inert gas pressures and aids understanding of biophysical factors in bubble formation and resolution. Such studies have uncovered the new phenomenon of continuous bubble formation in tissues and blood through "isobaric gas counterdiffusion."